Hey everyone, I'm so excited for the next three weeks at BLI. I can't wait to learn about molecular biology and finally be able to meet all of you. I am from Hopkinton, and am entering 10th grade after summer. Apart from school, during my free time I love to hang out with friends, play tennis, or volunteer at local farms and events. When I grow up, I have my mind set on being a pediatrican, so I want to prepare my self by learning about all the different aspects of biology during camp. See you all Monday!
Biological Research Final Project:
About Influenza:
Influenza, or more commonly known as the flu, severely sickens million of people each year, killing elderly and people with weakened immune systems on a constant basis.
The triangle diagram here shows the annual impacts of the flu since 2010, and these numbers were provided by CDC.
Screen Shot 2017-07-13 at 8.02.05 PM.png
Overall, there are four types of influenza viruses: A, B, C and D.
Even though there are four type, every year, typically only two flu subtypes circulating in humans: Influenza A and Influenza B. Doctors must design vaccines for the next year in order to combat Influenza A and B, but those vaccines are almost always, far from perfect.
Human influenza A, is the one I focused on, as it is most held responsible for causing seasonal epidemics of disease almost every winter in the United States. Influenza A can be transmitted by airborne respiratory droplets, skin to skin contact, by saliva or touching contaminated surfaces.
As you can see, the flu is a lot more damaging and contagious than we typically think. That’s why I choose to do my project on flu prevention. But before I go into my solution, here is some background knowledge on the flu.
How Contagious is the Flu?
One fact that you may not know is that you be able to pass on the flu to someone else before you even know you are sick. Some people can be infected with the flu virus but have no symptoms, yet still spread the virus to others.
For example: Most healthy adults may be able to infect other people beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. So even if enter a hospital during the winter especially, a good number of those people may have the flu and could get you sick.
Additionally, people with the flu can spread it to others up to, whom about 6 feet away.
How does the FLU make you sick: In order to get you sick, the flu cells must go through a complex process to infiltrate and start reproducing. In essence these are the steps the cell must undergo in order to spread disease:
The flu enters the body through the mucus membranes of your nose, eyes, or mouth.
The virus docks onto the surface of the cell membrane, allowing the cell to engulf the virus in a bubble and transports it towards the cell nucleus.
In order the release the virus, the virus’s capsid needs to be open. This is because, the few pieces of RNA that make up the genome of the flu virus are packed into a capsid, which keeps the virus stable when moving from cell to cell. The capsid also protects the viral genes against degradation.
However, in order for the virus to infect the host cell’s nucleus, the capsid of the flu virus needs to be cracked open. And to this is a really complicated process.
To achieve opening, the capsid of the influenza A virus imitates a bundle of protein waste – called an aggresome. Typically when detected, aggresome is disposed by the cell. However, since the flu virus is deceived as this aggresome protein waste, the cell’s disposal complex cracks open the capsid, as if it is aggresome, ultimately releasing the virus into the cell.
You might be wondering, how does the cell look like waste?
Essentially what happens is the virus capsid carries cellular waste ‘labels’ on its surface. These waste labels, called unanchored ubiquitin, calls an enzyme known as histone deacetylase (HDAC6) into action, which binds to ubiquitin, in a process called ubiquitination. This mechanical stress causes the capsid to tear, releasing the genetic material of the virus. Once the virus is within the nucleus, the cell starts to reproduce the viral genome and build new virus proteins.
Cracking the case takes about 20 to 30 minutes, as it is such a complex process.
The total infection period – from docking onto the cell’s surface to the RNA entering the cell nucleus – is two hours.
Back when this process was first discovered, it was observed that if the protein HDAC6 was absent, the flu infection was significantly weaker as the flu viruses did not have a central docking point for binding to the cell’s waste disposal system. However we cannot simply remove all HDAC6, as our body needs it. Solution: So the only way to prevent the flu from hijacking our cells, is to use a substance that prevents HDAC6 from binding to ubiquitin, in the ubiquitination process, without touching the enzyme in order to keep the capsid sealed and the flu locked in.
Screen Shot 2017-07-13 at 8.07.20 PM.png
Binding:
In ubiquitination, a protein is inactivated by attaching ubiquitin to it. Ubiquitin is a small molecule and it acts as a tag that signals that whatever ubiquitin is attached to needs to be degraded.
On ubiquitin, the carboxyl end of there is a glycine residue, or glycine amino acid, that makes up a side chain group of ubiquitin. This glycine residue, is responsibly the actual process of ubiquitination binding to a protein, as it actually attaches onto a specific target protein that needs degradation.
Like ubiquitin has a glycine residue, on typically every enzyme, there is lysine residue made up of a lysine amino acid, which is used to generate a bond to attach to the ubiquitin.
So, HDAC6 has 5 clusters of lysine, one of which being located in the C terminus, and thus allows for the bond to form between itself and ubiquitin.
That is how the ubiquitination works. So in order to prevent the flu infecting our cells, this bond needs to be prevented so that the ubiquitin will not bond to the HDAC6.
SOLUTION:
Screen Shot 2017-07-13 at 8.05.34 PM.png
Initially, a complex made up E3, a ligase enzyme, and E2, a conjuring enzyme will bond to HDAC6. In parallel, E1, an activating enzyme will activate Gene A only if it’s bonded target has been identified as HDAC6. This E1 enzyme activates Gene A by grabbing on Gene A, and dragging it over to the HDAC6. Now, E1 will bind to enzyme 2 in order to drop off Gene A nearby HDAC6, allowing a bond to form between HDAC6 and Gene A, Eventually a chain of Gene A will form to produce proteins that will attach to HDAC6 and release AASS and Serine hydroxymethyltransferase to degrade lysine and glycine.
Screen Shot 2017-07-13 at 8.08.50 PM.png
Screen Shot 2017-07-13 at 8.08.56 PM.png
Screen Shot 2017-07-13 at 8.09.52 PM.png
AIR Freshener Solution: My product will come in the form of an air freshener, as it is easy to use and very convenient.
Screen Shot 2017-07-13 at 8.11.54 PM.png
Summary: The flu is a very contagious sickness, that is a lot more harmful than we thought. In fact, patients with the flu, like Influenza A, can transmit the sickness before even showing symptoms. So as you can see, the flu is highly contagious is a health threat, especially in impoverished, crowded areas and or area in which unknown cases of flu is most commonly found: hospitals. In order to combat this problem, anyone can use this genetic air freshener to inhibit the flu from replicating within your body, even after inhalation. The spray does by retaining these components:
A gene that will mimic the C Terminal of ubiquitin and bond with HDAC6. Once bonded and identified the target as HDAC6, :
AASS Gene or α-aminoadipic semialdehyde synthase to degrade lysine
Serine hydroxymethyl transferase to degrade glycine
Upon using the spray, the HDAC6 will not be able to bind to ubiquitin, and thus the flu will not spread within our body.
Biological Research Final Project:
About Influenza:
How Contagious is the Flu?
One fact that you may not know is that you be able to pass on the flu to someone else before you even know you are sick. Some people can be infected with the flu virus but have no symptoms, yet still spread the virus to others.
For example: Most healthy adults may be able to infect other people beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. So even if enter a hospital during the winter especially, a good number of those people may have the flu and could get you sick.
How does the FLU make you sick:
In order to get you sick, the flu cells must go through a complex process to infiltrate and start reproducing.
In essence these are the steps the cell must undergo in order to spread disease:
- The flu enters the body through the mucus membranes of your nose, eyes, or mouth.
- The virus docks onto the surface of the cell membrane, allowing the cell to engulf the virus in a bubble and transports it towards the cell nucleus.
- In order the release the virus, the virus’s capsid needs to be open. This is because, the few pieces of RNA that make up the genome of the flu virus are packed into a capsid, which keeps the virus stable when moving from cell to cell. The capsid also protects the viral genes against degradation.
- However, in order for the virus to infect the host cell’s nucleus, the capsid of the flu virus needs to be cracked open. And to this is a really complicated process.
- To achieve opening, the capsid of the influenza A virus imitates a bundle of protein waste – called an aggresome. Typically when detected, aggresome is disposed by the cell. However, since the flu virus is deceived as this aggresome protein waste, the cell’s disposal complex cracks open the capsid, as if it is aggresome, ultimately releasing the virus into the cell.
- You might be wondering, how does the cell look like waste?
- Essentially what happens is the virus capsid carries cellular waste ‘labels’ on its surface. These waste labels, called unanchored ubiquitin, calls an enzyme known as histone deacetylase (HDAC6) into action, which binds to ubiquitin, in a process called ubiquitination. This mechanical stress causes the capsid to tear, releasing the genetic material of the virus. Once the virus is within the nucleus, the cell starts to reproduce the viral genome and build new virus proteins.
- Cracking the case takes about 20 to 30 minutes, as it is such a complex process.
- The total infection period – from docking onto the cell’s surface to the RNA entering the cell nucleus – is two hours.
Back when this process was first discovered, it was observed that if the protein HDAC6 was absent, the flu infection was significantly weaker as the flu viruses did not have a central docking point for binding to the cell’s waste disposal system. However we cannot simply remove all HDAC6, as our body needs it.Solution: So the only way to prevent the flu from hijacking our cells, is to use a substance that prevents HDAC6 from binding to ubiquitin, in the ubiquitination process, without touching the enzyme in order to keep the capsid sealed and the flu locked in.
Screen Shot 2017-07-13 at 8.07.20 PM.png
Binding:SOLUTION:
Screen Shot 2017-07-13 at 8.05.34 PM.png
Initially, a complex made up E3, a ligase enzyme, and E2, a conjuring enzyme will bond to HDAC6. In parallel, E1, an activating enzyme will activate Gene A only if it’s bonded target has been identified as HDAC6. This E1 enzyme activates Gene A by grabbing on Gene A, and dragging it over to the HDAC6. Now, E1 will bind to enzyme 2 in order to drop off Gene A nearby HDAC6, allowing a bond to form between HDAC6 and Gene A, Eventually a chain of Gene A will form to produce proteins that will attach to HDAC6 and release AASS and Serine hydroxymethyltransferase to degrade lysine and glycine.AIR Freshener Solution: My product will come in the form of an air freshener, as it is easy to use and very convenient.
Summary:
The flu is a very contagious sickness, that is a lot more harmful than we thought. In fact, patients with the flu, like Influenza A, can transmit the sickness before even showing symptoms. So as you can see, the flu is highly contagious is a health threat, especially in impoverished, crowded areas and or area in which unknown cases of flu is most commonly found: hospitals.
In order to combat this problem, anyone can use this genetic air freshener to inhibit the flu from replicating within your body, even after inhalation.
The spray does by retaining these components:
- A gene that will mimic the C Terminal of ubiquitin and bond with HDAC6. Once bonded and identified the target as HDAC6, :
- AASS Gene or α-aminoadipic semialdehyde synthase to degrade lysine
- Serine hydroxymethyl transferase to degrade glycine
Upon using the spray, the HDAC6 will not be able to bind to ubiquitin, and thus the flu will not spread within our body.Sources:
__https://en.wikipedia.org/wiki/Lysine__
__https://www.ncbi.nlm.nih.gov/books/NBK26818/__
__https://en.wikipedia.org/wiki/Glycine__
__https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=274__
__https://biocyc.org/HUMAN/NEW-IMAGE?type=PATHWAY&object=LYSINE-DEG1-PWY__
__https://en.wikipedia.org/wiki/HDAC6__
__http://www.nature.com/onc/journal/v26/n37/full/1210614a.html__
__https://www.ncbi.nlm.nih.gov/gene/10013__
__http://www.genecards.org/cgi-bin/carddisp.pl?gene=HDAC6__
__https://en.wikipedia.org/wiki/Ubiquitin__
__https://www.ebi.ac.uk/interpro/potm/2004_12/Page2.htm__
__http://www.medicinenet.com/script/main/art.asp?articlekey=26112__
__http://www.pnas.org/content/99/21/13425.full.pdf__
Link to Presentation:
https://docs.google.com/presentation/d/1of-YpIorBnJncWlaBAlvIz3Y-_zN2XP_N6cLn354cP0/edit?usp=sharing